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How Anthrax Toxin Kills

Recent concerns about bioterrorism have intensified interest in the bacterium Bacillus anthracis, the causative agent of anthrax. The pathogen's major virulence factor, lethal toxin (LT), is well characterized at the molecular level, but remarkably little is known about how it kills the infected host. One prevailing hypothesis suggests that lysis of B. anthracis-infected macrophages triggers the release of massive amounts of cytokines into the circulation, leading to endotoxic shock.

A new study raises questions about this pathophysiological model. Moayeri et al. injected LT into two strains of mice—one with toxin-sensitive macrophages, the other with toxin-resistant macrophages. Surprisingly, the two strains showed a similar course of disease, most notably characterized by the presence of hypoxia-induced liver damage and the absence of features typically associated with cytokine-induced shock. Thus, macrophage lysis is not essential for LT-induced death, and anti-cytokine therapies developed for septic shock may not be effective in patients with inhalation anthrax. — PAK